Pharmacokinetic evaluation of [<SUP>18</SUP>F]PR04.MZ for PET/CT imaging and quantification of dopamine transporters in the human brain

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dc.contributor.authorKramer, Vasko
dc.contributor.authorJuri, Carlos
dc.contributor.authorRiss, Patrick J.
dc.contributor.authorPruzzo, Rossana
dc.contributor.authorSoza-Ried, Cristian
dc.contributor.authorFlores, Jonathan
dc.contributor.authorHurtado, Ana
dc.contributor.authorRoesch, Frank
dc.contributor.authorChana-Cuevas, Pedro
dc.contributor.authorAmaral, Horacio
dc.date.accessioned2025-01-23T19:57:15Z
dc.date.available2025-01-23T19:57:15Z
dc.date.issued2020
dc.description.abstractPurpose Dopamine transporters (DAT) modulate pre-synaptic dopamine and physiological functions such as movement and reward. DAT also mirrors disease state in neurological disorders, rendering it an essential diagnostic target. [F-18]PR04.MZ is a new PET imaging agent for DAT with an improved affinity and selectivity profile, for which we here describe the complete pharmacokinetic evaluation in healthy controls. Methods Thirty-two healthy subjects underwent T1-weighted MRI and dynamic PET scans for 180 min with arterial blood sampling (n = 5) or 90 min without blood sampling (n = 25) after injection of 197.6 +/- 12.2 MBq [F-18]PR04.MZ. Blood and plasma metabolite analysis were performed. MRI-based normalization of brain images, delineation of VOIs, and kinetic modeling was conducted to determine distribution volumes (V-t) and binding potentials (BPnd). The impact of scan duration was evaluated and repeated PET scans were performed to assess test-retest variability (n = 5). A static imaging protocol has been validated for clinical applications. Results [F-18]PR04.MZ showed rapid metabolization in circulation, very high uptake in striatum and midbrain, and very low non-specific binding. The two-tissue compartment model 2TCM provided best fits for measured time-activity-curves and calculated V(t)s in putamen, caudate, substantia nigra pars compacta (SNpc), and cerebellar cortex were 11.83, 9.73, 2.12, and 0.57, respectively. All non-invasive models correlated well with BPnd values derived from 2TCM but underestimated DAT availability by about 28-33%. Of those, simplified reference tissue model (SRTM) provided the best fits, lowest Akaike Information Criteria values, and BPnd values of 14.82, 11.95, and 2.63 in putamen, caudate, and SNpc, respectively. BPnd estimates for striatal regions and SNpc were stable between 90 and 130 min post-injection. Test-retest results were excellent, showing low variability in all and excellent reliability in most relevant regions. Static imaging from 60 to 90-min post-injection is a viable alternative for quantification. Conclusions [F-18]PR04.MZ is a PET tracer with very high affinity, selectivity, and specific uptake in striatum and midbrain. 2TCM and SRTM provide good fits, high and stable V(t)s or BP(nd)s, and good test-retest reliability for precise quantification of DAT in human subjects.
dc.fuente.origenWOS
dc.identifier.doi10.1007/s00259-019-04594-z
dc.identifier.eissn1619-7089
dc.identifier.issn1619-7070
dc.identifier.urihttps://doi.org/10.1007/s00259-019-04594-z
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100732
dc.identifier.wosidWOS:000501498000001
dc.issue.numero8
dc.language.isoen
dc.pagina.final1937
dc.pagina.inicio1927
dc.revistaEuropean journal of nuclear medicine and molecular imaging
dc.rightsacceso restringido
dc.subject[F-18]PR04
dc.subjectMZ
dc.subjectPharmacokinetics
dc.subjectDopamine transporter
dc.subjectParkinson's disease
dc.subjectPET
dc.subjectCT
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePharmacokinetic evaluation of [<SUP>18</SUP>F]PR04.MZ for PET/CT imaging and quantification of dopamine transporters in the human brain
dc.typeartículo
dc.volumen47
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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